Ligelizumab for chronic spontaneous urticaria: a new star on the horizon

Results of a novel analysis of a previously published phase 2b trial, comparing ligelizumab with omalizumab in the treatment of chronic spontaneous urticaria (CSU), showed numerical superiority for ligelizumab in terms of speed of onset and duration of action [1,2].

Ligelizumab is a high-affinity, humanised, monoclonal, anti-IgE antibody, which has previously been assessed for treatment of patients with CSU who do not adequately respond to H1-antihistamines [1]. The phase 2b dose-finding trial (NCT02477332) with 382 patients did not only find superiority to placebo but also to omalizumab [1]. “In the present analysis we look at how long it takes before patients experience a beneficial response and how sustained this response is over the first 12 weeks of treatment,” Prof. Marcus Maurer (Charité Universitätsmedizin Berlin, Germany) told his audience [2]. For this purpose, 3 of the 6 treatment groups were separately analysed, namely ligelizumab 72 mg, ligelizumab 240 mg, and omalizumab 300 mg, all administered every 4 weeks.

Using an electronic diary, patients with moderate-to-severe CSU that were enrolled in the study collected their daily urticarial symptoms. This data was used to determine the Urticaria Activity Score summed over 7 days (UAS7). A UAS7 0 was defined as complete disease control and well-controlled disease as UAS7 1-6. As of week 2, numerically more participants in the 2 ligelizumab groups already reached a score of UAS7 0 than those treated with omalizumab. At week 12, UAS7=0 was achieved by 45.7% of participants treated with ligelizumab 72 mg, 43.6% of participants in the ligelizumab 240 mg arm, and 28.6% of participants in the omalizumab 300 mg arm. Overall, more patients reached the goal of a well-controlled disease (UAS7 1-6) in the ligelizumab groups. At week 2, the results were 43.4% for ligelizumab 72 mg, 36.1% for ligelizumab 240 mg, and 28.6% for omalizumab 300 mg. These results rose to 60.5% for ligelizumab 72 mg, 52.6% for ligelizumab 240 mg, and 51.9% for omalizumab 300 mg at week 12. Evaluating durability in terms of cumulative urticaria-free weeks over the duration of the study, the ligelizumab groups demonstrated mean values of 56.0% (72 mg) and 60.6% (240 mg) versus 38.1% with omalizumab.

Prof. Maurer concluded with 2 key messages based on these results: “Number 1, the onset of action with ligelizumab is faster than with omalizumab, with higher rates of patients achieving well-controlled and even completely controlled disease as soon as week 2. In addition to that, over the course of the first 12 weeks, patients experienced higher rates of complete control and well-controlled disease with ligelizumab than with omalizumab.” The ongoing phase 3 PEARL 1 (NCT03580356) and PEARL 2 (NCT03580369) studies will provide further efficacy and safety data of ligelizumab for up to 1 year.

1. Maurer M, et al. N Engl J Med. 2019;381:1321-32.
2. Maurer M, et al. Ligelizumab achieves fast control of symptoms in more patients with chronic spontaneous urticaria compared with omalizumab: analysis of the first 12 weeks of the Phase 2b study. FC08.10, EADV 2020 Virtual Congress, 29-31 Oct.

Posted on 17 December, 202018 December, 2020